Kinetics of Chromatid Aberrations in G2 Ataxia-telangiectasia Cells Exposed to X-rays and Ara A

Abstract

The cytogenetic effects of X-rays alone or in combination with 9-beta-D-arabinofuranosyladenine (ara A) were studied in an immortalized fibroblastic line of ataxia-telangiectasia (A-T) cells. The average length of G2 in this line was determined by autoradiographic labelling (labelled mitoses) to be approximately 5 h. Samples of A-T cells treated with or without ara A, 4 h prior to fixation were irradiated at 1/2-hourly intervals, from 1.5 h to 3.5 h before fixation and then examined for the presence of metaphase chromatid aberrations. It is postulated that the kinetics of disappearance (rejoining) of chromatid deletions with postirradiation incubation time reflects the underlying repair of dsb. This rejoining was found to be inhibited by ara A. Thus the frequency of deletions in the presence of ara A should represent the frequency of deletions in the absence of dsb repair. The rejoining kinetics for deletions in A-T was similar to that found in a previous study of normal human fibroblasts (Mozdarani and Bryant 1987). The number of deletions in X-irradiated A-T cells at 1.5 h before fixation was found to be higher by a factor of approximately 2 than that found previously in normals, indicating that in A-T a higher rate of conversion of dsb into chromatid deletions occurs. The frequency of exchanges induced in G2 A-T cells was similarly enhanced but, unlike the situation in normal cells, ara A was found to cause only a slight increase in this frequency.